Mo3Se4 nanoparticle with ROS scavenging and multi-enzyme activity for the treatment of DSS-induced colitis in mice

Ulcerative colitis (UC), as a most common inflammatory bowel disease (IBD), has become a global public health concern. Exploring novel method of treating UC is urgent and necessary. Recently, nanozyme with excellent antioxidant properties may be one useful therapeutic strategy. In this study, a two-dimensional transition metal chalcogenide (TMCs) nano flake and polyethylene glycol (PEG) modified Mo3Se4 nano flakes (PMNFs) was synthesized, which had multi-enzyme activity, including peroxidase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). The inhibition effect of PMNFs on sodium dextran sulfate (DSS)-induced colitis was explored. UC was effectively inhibited by PMNFs in this work. PMNFs significantly reduced disease activity index (DAI) score, including weight loss, colon shorten and histopathological abnormalities. The possible mechanism of PMNFs-attenuated colitis was investigated. The results showed that PMNFs reversed DSS-induced oxidative damage, and the antioxidant pathway Nrf2-keap1 signal was activated by PMNFs. Moreover, PMNFs suppressed the expression of pro-inflammatory factors including IL-1 beta, TNF-alpha, IFN-beta and IL-6 via the inactivation of TLR4/NF-kappa B pathway in DSS-induced colitis and LPS-treated macrophage. Furthermore, PMNFs treatment prevented the reduction of tight junction proteins (ZO-1, occludin, and claudin-1) and mucin-2 (MUC-2) as well as the up-regulation of epithelial apoptosis caused by DSS. These findings demonstrate that the PMNFs against DSS-induced colitis due to its prevention on oxidative damage, inflammation, and intestine barrier breakdown. Thus, PMNFs have a potential application in the treatment of various oxidative stress or inflammation-related diseases.

Automated summary

This study demonstrates that PMNFs have an inhibitory effect on ulcerative colitis by preventing oxidative damage, inflammation, and intestinal barrier breakdown. It activates the antioxidant pathway and suppresses the expression of pro-inflammatory factors, leading to the prevention of colitis. PMNFs also prevent the reduction of tight junction proteins and mucin-2 and the up-regulation of epithelial apoptosis caused by colitis. Thus, PMNFs have the potential to be applied in the treatment of various oxidative stress or inflammation-related diseases.